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Effects of Albumin/Furosemide Mixtures on Responses to Furosemide in Hypoalbuminemic Patients

NAGA CHALASANI^*, J. CHRISTOPHER GORSKI, JOHN C. HORLANDER, SR.^*, REBECCA CRAVEN, HELENA HOEN, JUAN MAYA and D. CRAIG BRATER

^* Division of Gastroenterology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Division of Biostatistics, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.

Correspondence to Dr. D. Craig Brater, Indiana University School of Medicine, 1120 South Drive, Fesler Hall 302, Indianapolis, IN 46202-5114. Phone: 317-274-8157; Fax: 317-274-8439; E-mail: dbrater{at}iupui.edu

Abstract. Hypoalbuminemic patients often have sufficient fluid accumulation to mandate diuretic therapy but are often resistant to diuresis. Studies have suggested that hypoalbuminemia itself impairs delivery of effective amounts of diuretic agent into the urine, the site of action. Therefore, administration of mixtures of albumin and loop diuretics may enhance responses. Thirteen patients with biopsy-proven cirrhosis and ascites (age, 51.2 ± 8.1 yr; Child-Pugh score, 8.5 ± 1.0; serum albumin concentration, 3.0 ± 0.6 g/dl) were studied in this randomized crossover study. Sodium balance was maintained throughout the study with a metabolic diet. All patients received spironolactone, but administration of all other diuretic agents was discontinued. Each patient received all of the following four treatments intravenously: (1) 40 mg of furosemide, (2) 25 g of albumin, (3) 40 mg of furosemide and 25 g of albumin premixed ex vivo, and (4) 40 mg of furosemide and 25 g of albumin infused simultaneously into different arms. Responses were assessed by measuring urinary sodium excretion and relating the urinary furosemide excretion rate to the sodium excretion rate. Additionally, the pharmacokinetics of furosemide were assessed. Furosemide pharmacokinetics were similar for all treatment arms. Albumin alone had negligible diuretic effects. Neither albumin regimen increased the response to furosemide. Moreover, the relationship between the urinary furosemide excretion rate and the sodium excretion rate was unaffected by albumin. In conclusion, albumin failed to enhance the diuretic effects of furosemide in cirrhotic patients with ascites. Therefore, the coadministration of albumin and furosemide for the treatment of cirrhosis, and likely other hypoalbuminemic conditions, should not be used clinically.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673